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PMID: 9560386 Published · ppublish English Journal Article Review

Rates of spontaneous mutation.

Genetics ·Vol. 148 ·No. 4 ·1998-04-00 ·Pages 1667-86

Drake JW, Charlesworth B, Charlesworth D, Crow JF

Abstract

Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates.

MeSH Terms
Animals Evolution, Molecular Humans Mutation
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Drake J W
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. [email protected]
Charlesworth B
Charlesworth D
Crow J F
References (99)
99 references, click to expand
  1. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli.
    Nature. 1996 Jun 20;381(6584):694-6 PMID: 8649513
  2. Detrimental genes with partial selfing and effects on a neutral locus.
    Genet Res. 1974 Apr;23(2):191-200 PMID: 4421247
  3. Genotype-environment interactions and the estimation of the genomic mutation rate in Drosophila melanogaster.
    Proc Biol Sci. 1994 Dec 22;258(1353):221-7 PMID: 7886063
  4. Rates of spontaneous mutation among RNA viruses.
    Proc Natl Acad Sci U S A. 1993 May 1;90(9):4171-5 PMID: 8387212
  5. Complete nucleotide sequence of the AIDS virus, HTLV-III.
    Nature. 1985 Jan 24-30;313(6000):277-84 PMID: 2578615
  6. Life with 6000 genes.
    Science. 1996 Oct 25;274(5287):546, 563-7 PMID: 8849441
  7. The complete genome sequence of Escherichia coli K-12.
    Science. 1997 Sep 5;277(5331):1453-62 PMID: 9278503
  8. A molecular approach to estimating the human deleterious mutation rate.
    Hum Mutat. 1993;2(3):229-34 PMID: 8364591
  9. Evolution of high mutation rates in experimental populations of E. coli.
    Nature. 1997 Jun 12;387(6634):703-5 PMID: 9192894
  10. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over.
    Nat Genet. 1996 Jul;13(3):336-42 PMID: 8673133
  11. The Caenorhabditis elegans unc-93 gene encodes a putative transmembrane protein that regulates muscle contraction.
    J Cell Biol. 1992 Apr;117(1):143-55 PMID: 1313436
  12. Evolution of the mutation rate at a heterotic locus.
    Proc Natl Acad Sci U S A. 1981 Apr;78(4):2452-4 PMID: 6941302
  13. Isolation and characterization of Escherichia coli antimutators. A new strategy to study the nature and origin of spontaneous mutations.
    Mol Gen Genet. 1985;201(2):315-22 PMID: 3003534
  14. Intron self-complementarity enforces exon inclusion in a yeast pre-mRNA.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12467-72 PMID: 9356473
  15. Spontaneous mutations accumulating in bacteriophage T4 in the complete absence of DNA replication.
    Proc Natl Acad Sci U S A. 1966 Apr;55(4):738-43 PMID: 5219679
  16. Mutation frequency in human blood cells increases with age.
    Mutat Res. 1995 Oct;338(1-6):141-9 PMID: 7565869
  17. Rates of spontaneous mutation in an archaeon from geothermal environments.
    J Bacteriol. 1997 May;179(10):3298-303 PMID: 9150227
  18. Spectra of spontaneous and mutagen-induced mutations in the lacI gene in transgenic mice.
    Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7958-62 PMID: 1832771
  19. Estimation of deleterious-mutation parameters in natural populations.
    Genetics. 1996 Sep;144(1):349-60 PMID: 8878698
  20. Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates.
    Genetics. 1991 Nov;129(3):957-62 PMID: 1752431
  21. Meiotic pachytene arrest in MLH1-deficient mice.
    Cell. 1996 Jun 28;85(7):1125-34 PMID: 8674118
  22. Mismatch repair deficiency in phenotypically normal human cells.
    Science. 1995 May 5;268(5211):738-40 PMID: 7632227
  23. ON THE TOPOGRAPHY OF THE GENETIC FINE STRUCTURE.
    Proc Natl Acad Sci U S A. 1961 Mar;47(3):403-15 PMID: 16590840
  24. Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses.
    Proc Natl Acad Sci U S A. 1985 Feb;82(3):677-81 PMID: 2983308
  25. The unc-22(IV) region of Caenorhabditis elegans: genetic analysis of lethal mutations.
    Genetics. 1988 Jun;119(2):345-53 PMID: 3396868
  26. Inbreeding depression and inferred deleterious-mutation parameters in Daphnia.
    Genetics. 1997 Sep;147(1):147-55 PMID: 9286675
  27. Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations.
    Proc Natl Acad Sci U S A. 1990 Aug;87(16):6019-23 PMID: 2201018
  28. The genetic variance for viability and its components in a local population of Drosophila melanogaster.
    Genetics. 1974 Dec;78(4):1195-208 PMID: 4218182
  29. CHROMOSOME NUMBER AND THE MUTATION RATE IN AVENA AND TRITICUM.
    Proc Natl Acad Sci U S A. 1929 Dec 15;15(12):876-81 PMID: 16587523
  30. Long-term results: cellulosic vs. synthetic membranes.
    Contrib Nephrol. 1995;113:120-34 PMID: 7712719
  31. Evolution of antigen drift/switching: continuously evading pathogens.
    J Theor Biol. 1994 Jun 7;168(3):291-308 PMID: 7520957
  32. Conjugation-dependent enhancement of induced and spontaneous mutation in the lacI gene of E. coli.
    Mol Gen Genet. 1985;201(1):35-7 PMID: 2997581
  33. Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli.
    J Bacteriol. 1997 Mar;179(5):1550-4 PMID: 9045812
  34. MSH2 deficient mice are viable and susceptible to lymphoid tumours.
    Nat Genet. 1995 Sep;11(1):64-70 PMID: 7550317
  35. Spontaneous mutation as a risk factor.
    Exp Clin Immunogenet. 1995;12(3):121-8 PMID: 8534499
  36. The Measurement of Gene Mutation Rate in Drosophila, Its High Variability, and Its Dependence upon Temperature.
    Genetics. 1928 May;13(4):279-357 PMID: 17246553
  37. Transposable elements in Drosophila melanogaster.
    Oxf Surv Eukaryot Genes. 1986;3:1-62 PMID: 2855303
  38. Fitness as a Measurable Character in Drosophila.
    Genetics. 1957 Jul;42(4):524-30 PMID: 17247713
  39. Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. II. Homozygous effect of polygenic mutations.
    Genetics. 1977 Nov;87(3):529-45 PMID: 200526
  40. Sequence of an unusually large protein implicated in regulation of myosin activity in C. elegans.
    Nature. 1989 Nov 2;342(6245):45-50 PMID: 2812002
  41. Mutation rates and dominance levels of genes affecting total fitness in two angiosperm species.
    Science. 1995 Jan 13;267(5195):226-9 PMID: 17791344
  42. Interaction between a putative mechanosensory membrane channel and a collagen.
    Science. 1996 Jul 19;273(5273):361-4 PMID: 8662524
  43. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1.
    J Gen Virol. 1988 Jul;69 ( Pt 7):1531-74 PMID: 2839594
  44. Evolutionarily stable mutation rate in a periodically changing environment.
    Genetics. 1989 Jan;121(1):163-74 PMID: 17246489
  45. Variation of spontaneous occurrence rates of chromosomal aberrations in the second chromosomes of Drosophila melanogaster.
    Genetics. 1974 Dec;78(4):1209-21 PMID: 4218183
  46. Nature of deleterious mutation load in Drosophila.
    Genetics. 1996 Dec;144(4):1993-9 PMID: 8978082
  47. Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human.
    Environ Mol Mutagen. 1995;25 Suppl 26:48-64 PMID: 7789362
  48. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer.
    Cell. 1995 Jul 28;82(2):321-30 PMID: 7628020
  49. The DNA of Caenorhabditis elegans.
    Genetics. 1974 May;77(1):95-104 PMID: 4858229
  50. Spontaneous mutation and parental age in humans.
    Am J Hum Genet. 1987 Aug;41(2):218-48 PMID: 3618593
  51. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis.
    Cell. 1995 Jul 28;82(2):309-19 PMID: 7628019
  52. Somatic mutation favors the evolution of diploidy.
    Genetics. 1995 Mar;139(3):1441-7 PMID: 7768451
  53. Evidence for a selectively favourable reduction in the mutation rate of the X chromosome.
    Nature. 1997 Mar 27;386(6623):388-92 PMID: 9121553
  54. Gamow-Teller strength in the 208Pb(p,n)208Bi reaction at 134.3 MeV.
    Phys Rev C Nucl Phys. 1989 Nov;40(5):1985-1992 PMID: 9966194
  55. Protein structural domains in the Caenorhabditis elegans unc-54 myosin heavy chain gene are not separated by introns.
    Proc Natl Acad Sci U S A. 1983 Jul;80(14):4253-7 PMID: 6576334
  56. Clusters of identical new mutation in the evolutionary landscape.
    Genetica. 1996 Oct;98(2):149-60 PMID: 8976063
  57. The high spontaneous mutation rate: is it a health risk?
    Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8380-6 PMID: 9237985
  58. Proliferation of mutators in A cell population.
    J Bacteriol. 1997 Jan;179(2):417-22 PMID: 8990293
  59. Fitness of third chromosome homozygotes in Drosophila melanogaster.
    Genet Res. 1975 Apr;25(2):197-200 PMID: 810388
  60. Comparing evolvability and variability of quantitative traits.
    Genetics. 1992 Jan;130(1):195-204 PMID: 1732160
  61. High mutation frequencies among Escherichia coli and Salmonella pathogens.
    Science. 1996 Nov 15;274(5290):1208-11 PMID: 8895473
  62. The evolution of multicompartmental genomes in viruses.
    J Mol Evol. 1987;25(4):277-81 PMID: 3118044
  63. Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis virus.
    J Virol. 1994 Jan;68(1):494-9 PMID: 8254760
  64. The mutational load with epistatic gene interactions in fitness.
    Genetics. 1966 Dec;54(6):1337-51 PMID: 17248359
  65. Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2.
    Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3122-7 PMID: 9096356
  66. Nucleotide sequence of tobacco mosaic virus RNA.
    Proc Natl Acad Sci U S A. 1982 Oct;79(19):5818-22 PMID: 6964389
  67. The genetic structure of natural populations of Drosophila melanogaster. XX. Comparison of genotype-environment interaction in viability between a northern and a southern population.
    Genetics. 1987 Oct;117(2):245-54 PMID: 3117620
  68. Genetic rearrangements occurring during a single cycle of murine leukemia virus vector replication: characterization and implications.
    J Virol. 1995 Dec;69(12):7991-8000 PMID: 7494312
  69. Bacteriophage T4 DNA polymerase mutations that confer sensitivity to the PPi analog phosphonoacetic acid.
    J Virol. 1993 Jan;67(1):60-6 PMID: 8380094
  70. Spontaneous mutational variances and covariances for fitness-related traits in Drosophila melanogaster.
    Genetics. 1996 Jun;143(2):829-37 PMID: 8725231
  71. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster.
    Genetics. 1972 Oct;72(2):335-55 PMID: 4630587
  72. The inbreeding decline and average dominance of genes affecting male life-history characters in Drosophila melanogaster.
    Genet Res. 1995 Feb;65(1):41-52 PMID: 7750745
  73. Replication infidelity during a single cycle of Ty1 retrotransposition.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7767-71 PMID: 8755550
  74. How much do we know about spontaneous human mutation rates?
    Environ Mol Mutagen. 1993;21(2):122-9 PMID: 8444142
  75. Chromatid structure: relationship between DNA content and nucleotide sequence diversity.
    Chromosoma. 1971 Mar 16;32(4):378-406 PMID: 4995642
  76. Rare variant alleles in the light of the neutral theory.
    Mol Biol Evol. 1983 Dec;1(1):84-93 PMID: 6599962
  77. Classification of hypotheses on the advantage of amphimixis.
    J Hered. 1993 Sep-Oct;84(5):372-87 PMID: 8409359
  78. Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation.
    EMBO J. 1997 Jun 2;16(11):3303-11 PMID: 9214645
  79. The Genetic Structure of Natural Populations of DROSOPHILA MELANOGASTER. VII Synergistic Interaction of Spontaneous Mutant Polygenes Controlling Viability.
    Genetics. 1969 Mar;61(3):749-61 PMID: 17248439
  80. Gene number, noise reduction and biological complexity.
    Trends Genet. 1995 Mar;11(3):94-100 PMID: 7732579
  81. Generation of genetic diversity in herpes simplex virus: an antimutator phenotype maps to the DNA polymerase locus.
    Virology. 1984 Jan 15;132(1):26-37 PMID: 6320535
  82. The infidelity of conjugal DNA transfer in Escherichia coli.
    Genetics. 1983 Nov;105(3):489-500 PMID: 6357941
  83. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.
    Cell. 1994 Jul 29;78(2):335-42 PMID: 7913883
  84. Spontaneous mutations in dry spores of Neurospora crassa.
    Z Vererbungsl. 1959;90:335-46 PMID: 13795075
  85. Genetic map of the Mycoplasma genitalium chromosome.
    J Bacteriol. 1995 Jun;177(11):3199-204 PMID: 7768819
  86. Adaptation of Drosophila melanogaster populations to high mutation pressure: evolutionary adjustment of mutation rates.
    Proc Natl Acad Sci U S A. 1987 Feb;84(4):1045-9 PMID: 3103121
  87. unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype.
    Genetics. 1980 Sep;96(1):147-64 PMID: 6894129
  88. Role of mutator alleles in adaptive evolution.
    Nature. 1997 Jun 12;387(6634):700-2 PMID: 9192893
  89. Low level of genetic drift in foreign sequences replicating in an RNA virus in plants.
    Virology. 1993 Jan;192(1):11-7 PMID: 8517013
  90. The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene.
    Nucleic Acids Res. 1980 Dec 20;8(24):5949-64 PMID: 6258156
  91. Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster.
    Genetics. 1978 Mar;88(3):575-90 PMID: 205482
  92. Mutation rate of the f episome.
    Science. 1995 Jul 21;269(5222):288-9 PMID: 17841227
  93. The minimal conserved transcription stop-start signal promotes stable expression of a foreign gene in vesicular stomatitis virus.
    J Virol. 1996 Apr;70(4):2318-23 PMID: 8642658
  94. Selection against hypermutability in Escherichia coli during long term evolution.
    Mol Gen Genet. 1984;198(2):177-8 PMID: 6394963
  95. Observations on two types of genetic instability in Escherichia coli.
    Acta Pathol Microbiol Scand. 1960;48:113-20 PMID: 14408281
  96. Parental origin effects, genome imprinting, and sex-ratio distortion: double or nothing?
    Am J Hum Genet. 1994 Dec;55(6):1073-5 PMID: 7977364
  97. Highly variable mutation rates in commensal and pathogenic Escherichia coli.
    Science. 1997 Sep 19;277(5333):1833-4 PMID: 9324769
  98. Incidence of mutator strains in Escherichia coli and coliforms in nature.
    Mutat Res. 1981 Mar;91(2):107-10 PMID: 7019693
  99. Deleterious mutations and the evolution of sexual reproduction.
    Nature. 1988 Dec 1;336(6198):435-40 PMID: 3057385
Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/148.4.1667
Email
[email protected]
Published
1998-04-00
Pages
1667-86
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1460098
Subset
IM
External Links
PubMed source DOI: 10.1093/genetics/148.4.1667 PMC Full Text View journal details
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